Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   18-JAN-08 Species laboratory mouse Generation N24+F4 (22-OCT-09)   Donating Investigator David Cohen,   Brigham and Women's Hospital

Description
Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. Protein product from the targeted gene is not detected in the liver cytosol of 8-day-old homozygous pups. The lipid content and composition of bile and lung surfactant secretions are normal in homozygous targeted mice. Plasma cholesterol and phospholipid levels are not affected in chow-fed homozygous targeted mutation mice, but there is an increase in the accumulation of small alpha-migrating high density lipoprotein (HDL) particles. Biliary concentrations of phospholipids, cholesterol, and bile salts are reduced in homozygous mutants as compared to wildtype mice when fed a high fat, high cholesterol, cholate-containing lithogenic diet. There is a greater hepatic accumulation of phospholipid and cholesterol in the targeted mutant animals. On the high fat diet, HDL particles are of normal size, but plasma cholesterol and phospholipid concentrations are increased compared to wildtype mice. This strain represents a model that may be useful in studies of lipid metabolism.

Development
A targeting vector containing a neomycin resistance gene was used to replace exons C and D by homologous recombination. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. The resultant strain has been backcrossed approximately twenty times to C57BL/6 by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pctp

000684	NZB/BlNJ
002105	NZO/HlLtJ
001058	NZW/LacJ

View Strains carrying other alleles of Pctp     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Pctp^tm1Bor/Pctp^tm1Bor

        B6.129P2-Pctp^tm1Bor

• cellular phenotype
• increased apoptosis (MGI Ref ID J:115284)
  • macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages
• immune system phenotype
• abnormal macrophage physiology (MGI Ref ID J:115284)
  • macrophages loaded with cholesteryl esters show impaired apoAI-mediated efflux of phospholipids and cholesterol compared to wild-type macrophages
  • macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Pctp^tm1Bor/Pctp^tm1Bor

        involves: 129P2/OlaHsd * FVB

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:57946)
  • mice do not exhibit defects in lipid metabolism, liver function or lung surfactant production

Pctp^tm1Bor/Pctp^tm1Bor

        involves: 129P2/OlaHsd * C57BL/6J

• liver/biliary system phenotype
• abnormal bile canaliculus morphology (MGI Ref ID J:115285)
  • in mutant livers, bile canaliculi show extensive branching at membrane surface
• abnormal gall bladder physiology (MGI Ref ID J:115285)
  • occlusion of gall bladder with mucin occurs at 7 days on a lithogenic diet compared to 18 hours on the FVB/NJ background
• abnormal bile composition (MGI Ref ID J:115285)
  • phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates
  • on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile
  • on a lithogenic diet, after 7 days, mice have 1.3 fold lower biliary cholesterol levels in bile compared to wild-type littermates
• gallstones (MGI Ref ID J:115285)
  • on a lithogenic diet, abundant liquid and solid cholesterol crystals that precede formation of macroscopic cholesterol gallstones are observed after 9 days
• homeostasis/metabolism phenotype
• abnormal bile salt level (MGI Ref ID J:115285)
  • on a lithogenic diet, TUDC concentration increases in mutants and controls, but remain higher in mutants; TC remains unchanged in mutants but increases in wild-type
  • relative concentration of tauromuricholate (TMC) is reduced and tauroursdeoxycholate (TUDC) and taurocholate (TC) concentrations are increased compared to control
  • bile salt concentrations are 1.3 fold lower than controls on lithogenic diets compared to mutants on the FVB/NJ background
• abnormal phospholipid level (MGI Ref ID J:115285)
  • phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates
  • on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile

Pctp^tm1Bor/Pctp^tm1Bor

        involves: 129P2/OlaHsd * FVB/NJ

• liver/biliary system phenotype
• abnormal bile canaliculus morphology (MGI Ref ID J:115285)
  • in mutant livers, bile canaliculi show extensive branching at membrane surface
  • bile canaliculi and junctional complexes appear more tortuous
• abnormal gall bladder physiology (MGI Ref ID J:115285)
  • occlusion of gall bladder with mucin occurs at 18 hours on a lithogenic diet
  • occlusion occurs much more quickly than on the C57BL/6J background
• abnormal bile secretion (MGI Ref ID J:115285)
  • bile flow rate is reduced by ~35% after 30 minutes in mutants on a regular chow diet
• homeostasis/metabolism phenotype
• abnormal bile salt level (MGI Ref ID J:115285)
  • bile salt concentrations are 4.3 fold higher than controls on regular chow diets
  • there is marked increase in bile salt secretion on chow diet
  • on lithogenic diet, concentration decreases; in wild-type, concentrations increase such that both genotypes have similar bile salt concentrations
  • on a chow diet, TC concentration is higher than controls, while other bile salt concentrations are reduced; on a lithogenic diet, percentage of TUDC is higher in mutants, but other types are similar in both mutants and controls
• decreased cholesterol level (MGI Ref ID J:115285)
  • on a lithogenic diet, biliary cholesterol levels decrease, but levels increase in wild-type
• increased cholesterol level (MGI Ref ID J:115285)
  • in chow-fed mice, biliary cholesterol levels are 5.9 fold higher than in controls

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pctptm1Bor
Allele Name		targeted mutation 1, Piet Borst
Allele Type		Targeted (knock-out)
Common Name(s)		Pc-tp -; Pctp-;
Mutation Made By		Michele Wu,   Brigham and Women's Hospital
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Pctp, phosphatidylcholine transfer protein
Chromosome		11
Gene Common Name(s)		PC-TP; STARD2;
Molecular Note		A neomycin selection gene replaced exons C and D by homologous recombination. Western blot analysis demonstrated that no detectable protein product was made in the cytosol of cells derived from homozygous mice. [MGI Ref ID J:57946]

Genotyping

Genotyping Information

Genotyping Protocols

Pctp^tm1Bor, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

van Helvoort A; de Brouwer A; Ottenhoff R; Brouwers JF; Wijnholds J; Beijnen JH; Rijneveld A; van der Poll T; van der Valk MA; Majoor D; Voorhout W; Wirtz KW; Elferink RP; Borst P. 1999. Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces. Proc Natl Acad Sci U S A 96(20):11501-6. [PubMed: 10500206]  [MGI Ref ID J:57946]

Additional References

Pctp^tm1Bor related

Baez JM; Tabas I; Cohen DE. 2005. Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein. Biochem J 388(Pt 1):57-63. [PubMed: 15628972]  [MGI Ref ID J:115284]

Scapa EF; Pocai A; Wu MK; Gutierrez-Juarez R; Glenz L; Kanno K; Li H; Biddinger S; Jelicks LA; Rossetti L; Cohen DE. 2008. Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2. FASEB J 22(7):2579-90. [PubMed: 18347010]  [MGI Ref ID J:138012]

Wang WJ; Baez JM; Maurer R; Dansky HM; Cohen DE. 2006. Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice. J Lipid Res 47(11):2400-7. [PubMed: 16940277]  [MGI Ref ID J:147028]

Wu MK; Cohen DE. 2005. Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice. Am J Physiol Gastrointest Liver Physiol 289(3):G456-61. [PubMed: 15845870]  [MGI Ref ID J:101230]

Wu MK; Cohen DE. 2005. Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins. Am J Physiol Gastrointest Liver Physiol 289(6):G1067-74. [PubMed: 16099870]  [MGI Ref ID J:104778]

Wu MK; Hyogo H; Yadav SK; Novikoff PM; Cohen DE. 2005. Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice. J Lipid Res 46(3):422-31. [PubMed: 15576839]  [MGI Ref ID J:115285]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   18-JAN-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.